Pyoderma Gangrenosum: A Critical
Appraisal
C M E
1 AMA PRA Category 1 CreditTM ANCC1.5 Contact Hours 0.5 Pharmacology Hours
Eran Shavit, MD & Dermatologist, Clinical Fellow & Division of Dermatology, Department of Medicine & Women_s College Hospital, University of Toronto & Toronto, Ontario, Canada
Afsaneh Alavi, MD, MSc, FRCPC & Assistant Professor & Division of Dermatology, Department of Medicine & Women_s College Hospital, University of Toronto & Toronto, Ontario, Canada
R. Gary Sibbald, MD, DSc (Hons), MEd, BSc, FRCPC (Med)(Derm), FAAD, MAPWCA & Professor & Medicine and Public Health & University of Toronto & Toronto, Ontario, Canada & Director & International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care) & Dalla Lana Faculty of Public Health & University of Toronto & Past President & World Union of Wound Healing Societies & Clinical Editor & Advances in Skin & Wound Care & Philadelphia, Pennsylvania
The authors, faculty, staff, and planners, including spouses/partners (if any), in any position to control the content of this CME activity have disclosed that they have no financial relationships with, or financial interests in, any commercial companies pertaining to this educational activity.
To earn CME credit, you must read the CME article and complete the quiz online, answering at least 13 of the 18 questions correctly. This continuing educational activity will expire for physicians on December 31, 2018, and for nurses on December 31, 2019.
All tests are now online only; take the test at http://cme.lww.com for physicians and www.nursingcenter.com for nurses. Complete CE/CME information is on the last page of this article. GENERAL PURPOSE:
To provide information about pyoderma gangrenosum (PG), including pathophysiology, diagnostic criteria, and treatment.
TARGET AUDIENCE:
This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.
LEARNING OBJECTIVES/OUTCOMES:
After participating in this educational activity, the participant should be better able to: 1. Recognize the pathophysiology of PG.
2. Select the diagnostic criteria for PG. 3. Identify the treatments available for PG.
DECEMBER 2017
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ABSTRACT
Pyoderma gangrenosum (PG) is an uncommon cutaneous disease, presenting with recurrent painful ulcerations most commonly on the lower extremities. The diagnosis is made according to a typical presentation, skin lesion morphology, skin biopsy, histopathology, and the exclusion of other etiologies. Classically, PG presents with painful ulcers with well-defined violaceous borders; other variants including bullous, pustular, and vegetative/granulomatous can also occur. Treatment of PG involves a combination of topical and systemic anti-inflammatory and immunosuppressive medications, wound care, antimicrobial agents for secondary infections, and treatment of the underlying etiology. This article is a continuing education review of the literature with a focus on the clinical application of the pathophysiology, diagnosis, and treatment of this challenging disease.
KEYWORDS:cutaneous disease, inflammatory bowel disease,
neutrophilic dermatosis, pyoderma gangrenosum, ulcer
ADV SKIN WOUND CARE 2017;30:534–42.
INTRODUCTION
Pyoderma gangrenosum (PG) is an uncommon ulcerative cu-taneous disease with a unique clinical presentation. It belongs to the neutrophilic dermatoses group of inflammatory derma-toses and is frequently associated with other systemic diseases. Despite the original unaltered term,pyoderma gangerenosum, this disease has no infectious etiology and no tissue-related vascular gangrene. Pyoderma gangrenosum usually occurs between 11 and 89 years of age, with a published case series reporting a mean age between 50 and 63 years (Table 1).1–6Fewer than 5% of PG
cases occur in children and infants. Associated systemic diseases
have been documented in 33% to 75% of patients.1–6
Comor-bidities most commonly associated with PG include inflamma-tory bowel disease (IBD), rheumatoid arthritis, other inflammainflamma-tory or autoimmune conditions, hematologic malignancy, and solid tumors.7–9
The skin biopsy of the edge of a PG lesion can result in nonspecific histopathology, especially when the disease is partially treated or minimally inflamed. The histopathologic presentation depends on the phase of the lesion sampled and the location of the biopsy. Generally, acute lesions have a dense neutrophilic infiltrate with or without very localized vasculitis changes. In Binus and colleagues_6retrospective series of 103
pa-tients, only 7% had a classic biopsy documented. This diagnosis is one of exclusion, requiring clinicopathologic correlation.7–9A
biopsy can help to rule out other diagnoses including primary vasculitis, other inflammatory conditions, infections, and malig-nancy. A biopsy of a subacute lesion of PG often demonstrates a
nonspecific mixed inflammatory infiltrate with the diagnosis made clinically, especially if a patient has a common associated systemic condition such as IBD, rheumatoid/seronegative arthritis, or hematopoietic malignancy.
The favored PG pathogenic hypothesis is autoimmune with defects in cell-mediated immunity, neutrophil and monocyte function, and humoral immunity. In addition, a patient_s genetic background can lead to aberrant activation of innate-immune complexes called inflammasomes. The activated immune system leads to increased levels of dermal cytokines and subsequent contribution to neutrophilic tissue infiltration. Pyoderma gangrenosum also can be induced by medications such as granulocyte colony-stimulating factor, isotretinoin, propylthiouracil, and sunitinib. In a recently published article, cocaine was found to be the most common agent to trigger a PG reaction.10
The management of PG is challenging, and a decision regard-ing the appropriate therapy depends on the location, number, size of the lesion(s), the course of the disease (indolent vs aggressive), and other factors, including associated morbidity. Depending on the extent and type of lesion, the treatment can be topical, intralesional, systemic anti-inflammatory (corticoste-roids), or immunosuppressive (cyclosporine). Targeted therapies including anti–tumor necrosis factor (TNF)! biologic agents have been used in the past few years, but newer targeted therapies may revolutionize the future management of PG.
METHODS
Information for this review was gathered from textbooks; PubMed, EMBASE, MEDLINE literature searches; and expert opinion. The PubMed, EMBASE, and MEDLINE searches
were performed using search words includingBpyoderma
gan-grenosum[ together with additional keywords such as Bpatho-physiology,[ Bmanagement,[ and Btherapy.[
The search included articles in English published between 1980 and 2017. A total of 2179 articles were found, including 504 review articles, 161 articles about management, 120 articles about pathophysiology, and 48 clinical trials. After narrowing the search terms to pathophysiology and management, only 30 ar-ticles were relevant and selected for inclusion.
RESULTS
Pathophysiology
The pathophysiology of PG is yet to be fully elucidated, but it is most likely a complex reaction pattern with convergent path-ways. Some of the factors contributing to the clinical manifes-tations of PG include neutrophil dysfunction, genetic mumanifes-tations, and abnormal inflammatory responses.
Table 1. SUMMARY OF 6 PYODERMA GANGRENOSUM CASE SERIES Re feren ce Case Seri es Von den Driesch et al 1(1997) Hasse lman n et al 2(2007) Saracin o et al 3 (2011) Binus et al 6(2011) Pereira et al 4 (201 3) Ye MJ (2014) 5 N o . o f patients 44 18 26 10 3 2 4 2 3 Fema les 30 (68% ) 14 (78%) 17 (65% ) 78 (76%) 19 (79% ) 16 (70%) M ales 14 (32% ) 4 (22% ) 9 (35% ) 25 (24%) 5 (21%) 7 (30% ) M ean age, y 50 (11– 80) 53 (26–78 ) 58 (SD, 25) 6 3 (3 0 – 8 9 ) Id iopathic 2 0 (45% ) 1 2 (67%) 27 (26%) 6 (25%) 12 (52%) As sociations 24 (55% ) 6 (33% ) 1 5 (58% ) 7 6 (74%) 18 (75% ) 1 1 (48%) In flamm atory bowel diseas e 1 4 (32% ) 2 (11% ) 4 (15% ) 3 5 (35%) 7 (29%) Oth er infl ammatory Rh eumato id arthri tis, di abetes mellitus, 2 (11% ) Rheu matoid arthri tis, 5 (19% ) Sero negat ive arthri tis, 20 (1 9%) 3 (12%) H ematologic abn ormalities/ m alignanci es 10 (23% ) M onoclonal gamm opathies 2 (11% ) 21 (20%) 6 (25%) So lid tumo rs Additional asso ciations: pso rias is, 11 %; he pa titis, 9% 2 (8%) Site : legs Predilection 17 (74%) 13 (57% ) U lcer type 15 (63%) 18 (78% ) Bu llous 2 (8%) 2 (9%) Pustu lar 4 (17%) 1 (4%) Vege tative/gra n u loma tou s 1 (4%) 2 (9%) Les ions Sin gle 23 (52% ) 15 (63% ) M ultiple 21 (48% ) 9 (37%) M ortality 8 /4 2 fo llo w -u p = 19% 1 (6 % ) (s h o rt fo llo w -u p ) 27% 10 % 5 (22% ) Numbers have been rounded to the nearest whole numb er.
The presence of clonal T-cell expansion has been reported in PG lesions, supporting the possibility of an aberrant T-cell
re-sponse.11 Inflammasomes are multiprotein oligomers often
expressed in myeloid cells and keratinocytes. They may be in-volved in the recruitment or activation of polymorphonuclear neutrophils, as seen in cases associated with a mutation in the genePSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) on chromosome 15. A mutation inJAK2 (Janus kinase 2), a nonreceptor tyrosine kinase involved in signaling via several cytokines, has also recently been identified in patients with PG.12,13 Elevated levels of inflammatory mediators have been detected in lesions of PG, suggesting a pathologic inflammatory process. T cells and macrophages likely play a key role in the PG disease pathogenesis via abnormal cytokine signaling.11
Interleukin 23 (IL-23), a cytokine that plays an important role in driving IL-17–mediated and neutrophil-rich inflammation, is up-regulated at the gene expression and protein level in PG lesions. This suggests pathogenic similarities with other inflam-matory diseases, including psoriasis.14
Clinical Forms of PG and Its Variants
Four morphologic PG variants are known: 1. ulcerative
2. vesicular-bullous (atypical) 3. pustular
4. superficial granulomatous/vegetative.
Postsurgical PG and peristomal PG usually present with an ulcerative morphology. Each PG variant has different clinical presentations and systemic associations (see Supplemental Digital Content 1, http://links.lww.com/NSW/A10, and Figures 1, 2, and 3).
The vesicular-bullous variant presents on the face and the upper extremities, especially the dorsal hands. Clinical presen-tation overlaps with the superficial bullous variant of the neu-trophilic dermatosis Sweet syndrome (often with fever and arthralgias) that can occur most often in the setting of infections, drug use, or acute myelogenous leukemia.
The pustular type consists of multiple, small, sterile pus-tules. These pustules usually regress without scarring, but can evolve into classic PG. This form is most commonly reported in patients with IBD, but a similar eruption may be seen in patients with Behc¸et disease or as an inflammatory bowel– associated dermatosis.
The superficial granulomatous or vegetative type is a rare, usually more benign variant that favors the trunk and often follows trauma (eg, postsurgery). There is a superficial erosion or ulceration with heaped-up, often necrotic, margins. Micro-scopic examination of a skin biopsy will reveal less intense neutrophilic infiltrate with a more characteristic suppurative
and granulomatous histology. It is clinically unlikely to be associated with an underlying disease and responds to less aggressive therapy.
Clinical variants have been described based on the clinical presentation or the location of the lesion. Extra mucocutane-ous sterile neutrophilic infiltrate has been reported in the bones, lung, liver, pancreas, spleen, kidneys, and central nervous system of patients with PG.15,16
Pyoderma Gangrenosum and Associations
Pyoderma gangrenosum is a common extracutaneous man-ifestation of IBD, more commonly associated with ulcerative colitis (5%–12%) than Crohn disease (1%–2%). Between 50% and 75% of patients with PG have an antecedent, coincident, or subsequent associated disease or condition. In a systematic literature review, DeFilippis et al17reviewed 208 articles
describ-ing 823 cases of PG. Thus far, the correlation of the appearance of PG with IBD activity is still controversial,18-20although individual
patients may have PG associated with IBD activity. In addition, PG does not always clear upon treatment of the underlying bowel disease, and response to surgical resection of the abnor-mal bowel is unpredictable.20
The other common associated disorders include arthritic and hematologic disorders. In a retrospective study6of 103 patients with PG (74% with an associated systemic disease, including IBD [35%]), 20% had hematologic disorders, 19% had seronegative arthritis, and 26% were idiopathic.
Figure 1.
PYODERMA GANGRENOSUM WITH UNDERMINED BORDER AND SOME NECROTIC TISSUE IN ULCER BED
Courtesy of Dr Afsaneh Alavi.
Pyoderma gangrenosum plus syndromes:PG has been described clinically with other inflammatory disorders, including syndrome combinations with
& PASH: PG, acne, and suppurative hidradenitis
& PAPASH: PG, acne, pyogenic arthritis, and suppurative hidradenitis & PsPASH: Psoriatic arthritis, PG, acne, and suppurative hidradenitis & PAC: PG, acne, and ulcerative colitis
& PAPA: PG, acne, and pyogenic arthritis & PASS: PG, acne, and spondyloarthritis
The rarity of these syndromes complicates the establishment of evidence-based treatment guidelines. They all share a com-mon pathogenesis involving a dysregulated innate immune sys-tem with abnormal IL-1 signaling leading to sterile neutrophilic inflammation. Treatment can be challenging because of a lack of response to standard treatment modalities.13,21,22
Diagnosis
The diagnosis of PG is clinical and requires the exclusion of other disorders in the differential diagnosis. The histopathol-ogy is nonspecific for this disease, and it serves to rule out other pathologic findings. Nevertheless, the classic histologic presen-tation is neutrophil-rich cell infiltrate in the dermis, but this is limited to early lesions. Pyoderma gangrenosum also does not have a specific laboratory workup. The differential diagnosis should include not only unique infections such as deep fungus infection (especially North American blastomycosis) and myco-bacterial infections, but also other noninfectious etiologies such as bromoderma or iododerma.
(The Table Supplemental Digital Content 1, http://links.lww. com/NSW/A10) lists relevant workup and differential diagnoses providers should consider. The main emphasis should be on obtaining a thorough medical history and meticulous physical examination to enhance the clinical investigation and diagnosis. However, there is no internationally accepted diagnostic crite-rion for PG. In 2004, Su et al23proposed diagnostic criteria where both major criteria and at least 2 minor criteria (out of 4) are required to establish the diagnosis. One of the major criteria is the exclusion of other causes of cutaneous ulceration (Table 2).
The pain associated with PG can be consistent with more than 1 type of wound; however, there are 2 types of ulcers that may cause excruciating pain and are confined to the lower ex-tremities, including arterial ulcers and Martorell (hypertensive
Figure 2.
MORE EXTENSIVE BUT SUPERFICIAL ULCERATION
Courtesy of Dr Afsaneh Alavi.
Figure 3.
POSTSURGICAL PYODERMA GANGRENOSUM
Courtesy of Dr Afsaneh Alavi.
Table 2.
PROPOSED DIAGNOSTIC CRITERIA FOR PYODERMA
GANGRENOSUM22
Major Criteria
1. Rapid progression of a painful, necrolytic, cutaneous ulcer with an irregular, violaceous border
2. Exclusion of other causes of cutaneous ulceration Minor Criteria
1. History suggestive of pathergy or clinical finding of cribriform scarring
2. Systemic diseases associated with pyoderma gangrenosum 3. Histopathologic findings compatible with pyoderma gangrenosum
ischemic) ulcers. Arterial ulcers present in the shins (usually in pressure-dependent areas) and are deep, punched-out ulcers with a fibrous base. Clinically weaker or absent pulses are noticed. Martorell ulcers are typically located on the lateral-dorsal side of the shins and are morphologically shallower ne-crotic ulcers; pulses are usually palpable and normal.24–26
Management
The main goal of therapy is to reduce the inflammatory pro-cess of PG that leads to ulceration. The choice of treatment depends on various factors including the number and size of the lesions, their location, the presence of underlying disease, and patient preference and comorbidities. Although treatment of the underlying disease is essential, a direct relationship be-tween the severity of associated disease and PG is debatable.
Treatment also depends on the course of the disease. Roughly, PG can be divided into an aggressive type with a rapid course and the indolent form with a more protracted and slower, chronic course. Often, the latter only requires localized therapy. Systemic therapy includes high-dose corticosteroids as first-line therapy, while cyclosporine and TNF-! inhibitors have proved useful as second- and third-line therapies. For patients with limited disease, topical and intralesional corticosteroids may give sufficient results without the necessity of systemic therapy.27Other topical agents include topical tacrolimus (which proved useful in a small sample prospective study28); other reported treatments include sodium cromoglycate, nicotine, and topical dapsone (based on case reports or small case series).29Alavi et al30recently suggested an approach for treatment based on patient course, as shown in Table 3.
Table 3.
DIAGNOSTIC ALGORITHM FOR PYODERMA GANGRENOSUM
Complete History and Physical Examination, Skin Biopsy
Pyoderma Gangrenosum Workup Guided by History Main Differential Diagnosis
Categories Main Differential Diagnosis Examples Workup Infection Deep fungal infection: blastomycosis,
sporotrichosis
Cultures, special stains, chest radiograph
Protozoa: leishmaniasis Bacterial: ecthyma Viral: herpes simplex Vasculitis and autoimmune
diseases
Behc¸et disease Blood work, coagulopathy panel, urinalysis Vasculitis ANA, anti-DNA, ENA, rheumatoid factor, C3, C4 Cryoglobulinemia Direct immunofluorescence (skin biopsy) Antiphospholipid syndrome
Lupus (lupus-associated neutrophilic dermatoses)
Neutrophilic dermatoses Sweet syndrome Mainly a clinical diagnosis (and histology) ASOT, CRP, CBC
Check for possible drug etiology
Vascular disorders Martorell ulcer Deep elliptical biopsy, Doppler study, ABI or angiography, venous Duplex
Arterial ulcer Venous ulcer
Exogenous Factitious History, serum bromide, and iodide Brown recluse spider bite
Bromoderma
Abbreviations: ANA, antinuclear antibody; ABI, ankle brachial index; ASOT, aspartate aminotransferase; C3, C4, complement factors 3, 4; CBC, complement blood count; CRP, C-reactive protein; ENA, extractable nuclear antigen.
Other important aspects of treatment are pain control and local wound care. Pain management is an essential part of man-aging patients with PG. It should be addressed initially with oral administration of acetaminophen and nonsteroidal anti-inflammatory drugs for nociceptive pain (gnawing, aching, tender, and/or throbbing pain), then as necessary mild opioids such as codeine, then strong opioids such as morphine, until the patient is free of pain.31Initial treatment of neuropathic pain (burning, stinging, shooting, or stabbing) can be managed with gabapentin and pregabalin, along with nortriptyline at night to facilitate sleep. Optimal wound care includes cleansing and preventing secondary infections and the appropriate utilization of anti-bacterial agents in the presence of localized infection, because the prevention of deep, surrounding infection is more impor-tant than tissue toxicity from the antiseptic agents.30
Maintain-ing a moist wound environment is a basic principle of wound therapy. Conservative debridement (enzymatic, autolytic, or blunt surgical) to remove nonviable tissue should be per-formed with caution, as PG is both induced and aggravated by pathergy (minimal trauma leads to extension of the le-sions). The pathergy skin test is a hypersensitivity reaction to a skin prick and can be elicited by poking the skin with a needle or a pin and is considered a specific presentation in neutrophilic dermatoses.32
Systemic corticosteroids are still considered to be the first-line therapy for severe, progressive disease.33The treatment can be ad-ministered orally (0.5–1.0 mg/kg per day) or intravenously (100 mg/d). Rapid response should be expected.34
Cyclosporine (2.5–5.0 mg/kg per day) is frequently used as second-line treatment and may be effective as a steroid-sparing agent and is especially useful in cases resistant to corticosteroids. A recently published randomized controlled study35
com-pared oral prednisolone (0.75 mg/kg per day) with cyclosporine (4 mg/kg per day) to a maximum dose of 75 mg and 400 mg/d, respectively, on 121 patients with PG. Both groups demonstrated the same outcome, with fewer than half of patients in either group completely healing. Other immunosuppressive medica-tions including methotrexate, azathioprine, mycophenolate mofetil, and sulfasalazine have been suggested as clinical alternatives for PG, but have not been the subject of controlled studies.36
Future treatment of PG may include biologic agents. High levels of TNF-! associated with neutrophilic infiltration charac-terize PG as well as other inflammatory processes,21,37so
tar-geted biologic therapies such as anti–TNF-! medications may therefore expand the therapeutic options. The TNF-! antagonists (etanercept, adalimumab, infliximab) have mostly been stud-ied in case reports and small case series treating PG. One randomized controlled study performed on infliximab showed
benefit for this medication in 70% of patients; however, this was a small study, completed with just 30 patients.38The anti–
IL-12/IL-23 ustekinumab is the only IL-23 inhibitor reported
to improve PG.39,40 A patient with psoriasis treated with
adalimumab who developed PG was successfully treated with ustekinumab.39
Interleukin 1", a potential proinflammatory cytokine, was demonstrated to be overexpressed in lesional skin of patients with PG, which is the rationale for a potential role of IL-1
antagonists in the management of PG.41 Canakinumab, a
human anti–IL-1" monoclonal antibody, demonstrated ben-efit in a recently published article on 5 patients with corticosteroid-refractory PG.42Anakinra, a recombinant, on-glycosylated form of
IL-1 receptor antagonist used to treat RA and cryopyrinopathies (rare inherited autoinflammatory disorders that are caused by mutations inCIAS1 [cold-induced autoinflammatory syndrome 1] gene encoding the cryopyrin protein), elicited low therapeutic efficacy in 3 studies.43–45
Other new targeted therapies, including anti–IL-6 (tocilizumab), were successful as described in a case report on a patient with rheumatoid arthritis and PG.46Additional agents including anti– IL-17 medications (eg, secukinumab, ixekizumab) may be good choices for future investigation (Table 4).
CONCLUSIONS
Pyoderma gangrenosum is a neutrophilic dermatosis. Diag-nosis is made based on the characteristic clinical picture and the exclusion of other diseases. In up to two-thirds of cases, PG is associated with an underlying disease, and therapy should aim to treat both PG and the associated condition. Autoinflammatory diseases are clinically characterized by recur-rent episodes of sterile inflammation in the affected organs, without high titers of circulating autoantibodies and autoreactive T cells. These conditions are associated with many genetically determined alterations of the innate immune response, inducing an overproduction of active IL-1" that can lead, via the release of several proinflammatory cytokines and chemokines, to neutrophil-mediated inflammation.
Treatment of PG should involve a combination of anti-inflammatory (oral, intralesional, topical steroids) with immuno-suppressive (oral cyclosporine) medications as well as antibiotics for secondary infections, topical medications (topical tacrolimus, pimecrolimus), and wound care (conservative debridement of active lesions to prevent pathergy, topical anti-inflammatories/ antimicrobials, and moisture balance).
Further patient studies are necessary to establish universally accepted diagnostic criteria for PG and elucidate the exact pathophysiology and optimal treatment of this disease.
PRACTICE PEARLS
REFERENCES
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THERAPEUTIC APPROACH TO PYODERMA
GANGRENOSUM28
Approach Management
General measures Control underlying disease Avoid trauma
Pain management Proper local wound care Control of secondary infection Minimize edema (compression therapy) Optimize nutrition
Smoking cessation Glycemic control Limited disease Topical therapy
Potent topical corticosteroids Intralesional corticosteroids Topical tacrolimus, pimecrolimus Topical sodium cromoglycate Topical dapsone Topical nicotine 5-aminosalicylic acid Aggressive disease (systemic therapy) Corticosteroids (0.1–1.0 mg/kg OD) Cyclosporine (2.5–5.0 mg/kg OD) Tacrolimus (0.1–0.2 mg/kg OD) Thalidomide (50–150 mg QHS) Colchicine (0.6–1.2 mg OD) Dapsone (100 mg OD) Sulfasalazine (0.5–1.0 g TID) Azathioprine (50–100 mg BID) Methotrexate (2.5–25 mg weekly) Mycophenolate mofetil (1.0–1.5 g BID) Chlorambucil (4.6 mg OD)
Intravenous immunoglobulin (2.0–3.0 g/kg) Minocycline (100 mg OD)
Aggressive disease (targeted therapy)
Anti–tumor necrosis factor Infliximab Adalimumab Etanercept Anti–interleukin 1 Anakinra Canakinumab Gevokizumab Anti–interleukins 12 and 23 Ustekinumab
Abbreviations: BID, twice daily; OD, once daily; QHS, every night; TID, 3 times daily.
& Pyoderma gangrenosum is an ulcerative skin disease with unique clinical presentations.
& The classic ulcerative variant usually presents on the legs with a deep erythematous painful ulcer and undermined bor-ders, although there are other forms: pustular, bullous, and vegetative/granulomatous.
& Diagnosis of PG is made based on a classic clinical presentation and exclusion of other causes.
& It is associated with underlying etiologies; IBD is the most common. Arthritis (rheumatoid, seronegative) and myelo-proliferative disorders need to be identified or ruled out. & Treatment should address underlying disorders and spe-cifically be based on anti-inflammatory/immunosuppressive medications.
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17. DeFilippis EM, Feldman SR, Huang WW. The genetics of pyoderma gangrenosum and implications for treatment: a systematic review. Br J Dermatol 2015;172(6):1487-97. 18. Weizman AV, Huang B, Targan S, et al. Pyoderma gangrenosum among patients with inflam-matory bowel disease: a descriptive cohort study. J Cutan Med Surg 2015;19(2):125-31. 19. Greuter T, Navarini A, Vavricka SR. Skin manifestations of inflammatory bowel disease
[published online ahead of print June 23, 2017]. Clin Rev Allergy Immunol. 20. Menachem Y, Gotsman I. Clinical manifestations of pyoderma gangrenosum associated
with inflammatory bowel disease. Isr Med Assoc J 2004;6:88-90.
21. Marzano AV, Borghi A, Meroni PL, Cugno M. Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation. Br J Dermatol 2016;175(5):882-91. 22. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)? A new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol 2012;66(3):409-15.
23. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 2004;43(11):790-800. 24. Weenig RH, Davis MD, Dahl PR, Su WD. Skin ulcers misdiagnosed as pyoderma
gangre-nosum. N Engl J Med 2002;347(18):1412-8.
25. Su WD, Duncan SC, Perry HO. Blastomycosis-like pyoderma. Arch Dermatol 1979;115(2): 170-3.
26. Alavi A, Mayer D, Hafner J, Sibbald RG. Martorell hypertensive ischemic leg ulcer: an underdiagnosed entity. Adv Skin Wound Care 2012;25(12):563-72.
27. Keltz M, Lebwohl M, Bishop S. Peristomal pyoderma gangrenosum. J Am Acad Dermatol 1992;27(2):360-4.
28. Marzano AV, Trevisan V, Lazzari R, Crosti C. Pyoderma gangrenosum: study of 21 patients and proposal of aFclinicotherapeutic_ classification. J Dermatol Treat 2011;22(5):254-60. 29. Handler M, Hamilton H, Aires D. Treatment of peristomal pyoderma gangrenosum with
topical crushed dapsone. J Drugs Dermatol 2011;10(9):1059-61.
30. Alavi A, French LE, Davis MD, Brassard A, Kirsner RS. Pyoderma gangrenosum: an update on pathophysiology, diagnosis and treatment. Am J Clin Dermatol 2017;18(3):355-72. 31. Sibbald RG, Goodman L, Woo KY, et al. Special considerations in wound bed preparation
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For more than 153 additional continuing education articles related to Skin and Wound Care topics, go to NursingCenter.com/CE.
CONTINUING MEDICAL EDUCATION INFORMATION FOR PHYSICIANS
Lippincott Continuing Medical Education Institute, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Lippincott Continuing Medical Education Institute, Inc. designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only the credit
commensurate with the extent of their participation in the activity.
PROVIDER ACCREDITATION INFORMATION FOR NURSES
Lippincott Professional Development will award 1.5 contact hours which includes 0.5 hour of pharmacology for this continuing nursing education activity.
LPD is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.
This activity is also provider approved by the California Board of Registered Nursing, Provider Number CEP 11749 for 1.5 contact hours. LWW is also an approved provider by the District of Columbia, Georgia, and Florida CE Broker #50-1223.
OTHER HEALTH PROFESSIONALS
This activity provides ANCC credit for nurses and AMA PRA Category 1 CreditTM
for MDs and
DOs only. All other healthcare professionals participating in this activity will receive a certificate of participation that may be useful to your individual profession’s CE requirements.
CONTINUING EDUCATION INSTRUCTIONS
&
Read the article beginning on page 534. For nurses who wish to take the test for CE contact hours, visit http://nursing.ceconnection.com. For physicians who wish to take the test for CME credit, visit http://cme.lww.com. Under the Journal option, select Advances in Skin and Wound Care and click on the title of the CE activity.&
You will need to register your personal CE Planner account before taking online tests. Your planner will keep track of all your Professional Development online CE activities for you.&
There is only one correct answer for each question. A passing score for this test is 13 correct answers. If you pass, you can print your certificate of earned contact hours or credit and access the answer key. Nurses who fail have the option of taking the test again at no additional cost. Only the first entry sent by physicians will be accepted for credit.Registration Deadline: December 31, 2019 (nurses); December 31, 2018 (physicians).
PAYMENT
